The objective of this research is to study various facets of carbohydrate metabolism (with particular emphasis on the sorbitol pathway) in both human and rabbit intact lenses by carbon-13 and phosphorous-31 nuclear magnetic resonance spectroscopy. The use of NMR spectroscopy provides an opportunity to study directly the molecular dynamics of cataractogenesis in a single human lens caused by high sugar levels. This may lead to a more clear understanding of the biochemistry of this pathology and thus to a medical treatment. It also provides a means of testing directly the efficacy of such drugs. Our specific aims are as follows: (i) Determination of the metabolic fluxes of the sorbitol pathway, anerobic glycolysis, and the pentose phosphate pathway; (ii) investigation of the dynamics of lenticular pH changes; (iii) determination of bioenergetic metabolic fluxes (ATP, ADP, AMP, Pi, NAD+, phosphocreatine, alpha-glycerophosphate); (iv) determination and delineation of the point of irreversible damage under temporary insults of low and high glucose levels; (v) determination of the effect of Aldose Reductase inhibitors on lens metabolic fluxes. Normal, diabetic, and cataractous lenses (non-diabetic and diabetic) will be employed. We are particularly interested in the interrelationships of the various metabolic fluxes, i.e., in facets of control and regulation of lenticular metabolic processes under normal as well as stressful conditions, and how they relate to cataractogenesis in the human lens.